Ahmedzai, S., & Brooks, D. (1997). Transdermal fentanyl versus sustained-release oral morphine in cancer pain: Preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. Journal of Pain and Symptom Management, 13, 254–261.

To compare transdermal fentanyl and sustained-released morphine in palliative care patients with cancer by measuring efficacy, tolerance, and quality of life (QOL).

Patients received one treatment for 15 days, then the other for 15 days to compare which provided the greatest efficacy and QOL, and the fewest side effects. The null hypothesis was 50% of patients would prefer fentanyl and 50% would prefer morphine.

• The study reported on a sample of 202 adult palliative care patients with cancer; 110 completed the study.
• Mean patient age was 61.5 years.
• The sample was 55% male.
• Patients had a life expectancy greater than a month and were receiving a strong, stable dose of opioids.

38 different palliative care centers in the United Kingdom

This was a randomized, open, two-period, crossover study.

• QOL was assessed with World Health Organization (WHO) performance status (measured prestudy, post-study, and daily during the study) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire, which measures side effects, convenience, and effects on activities of daily living (ADLs) or careers (measured after each arm of the study). These tools have been validated for patients with advanced cancer. 
• Constipation and diarrhea were assessed with the EORTC scale prestudy and on days 8, 16, 23, and 31. 
• Daily diaries were used to record estimated sleep length, night awakening, daytime drowsiness, and use of rescue medications.
• Memorial Pain Assessment Card was used BID for assessment of pain and mood.
• Skin assessment was performed when removing patches.

• The top reason patients withdrew from the study was because of adverse events.
• Fentanyl was associated with significantly less constipation than morphine (p <  0.001). This was confirmed through multiple assessment mechanisms.
• The remaining results did not pertain to constipation.

• Patients were allowed short-acting morphine for breakthrough pain, which could alter the results for fentanyl; however, the results were still significant.
• Having a \"washout\" period is unethical.
• Some patients may have dropped out because of morphine withdrawal.
• The study was not blinded; therefore, bias may exist according to delivery mechanism preference.
• Fentanyl and morphine doses varied among individuals and were titrated, as needed, throughout the study.